Genetic variation in neuropeptide Y interacts with childhood trauma to influence anxiety sensitivity.

Background And Objectives: Anxiety sensitivity (AS) refers to a fear of the negative implications of anxiety, and arises due to gene-environment interactions. We investigated whether genetic variation in two neuropeptides implicated in the stress response, neuropeptide Y (NPY) and pituitary adenylate cyclase-activating polypeptide receptor 1, interacted with childhood trauma (CT) to influence AS.

Design And Methods: This cross-sectional study examined the CT x genetic variant effects on AS in 951 adolescents who self-identified as Xhosa or South African Colored (SAC) ethnicity.

Antenatal Uterotonics as a Risk Factor for Intrapartum Stillbirth and First-day Death in Haryana, India: A Nested Case-control Study.

Background: Use of uterotonics like oxytocin to induce or augment labor has been shown to reduce placental perfusion and oxygen supply to the fetus, and studies indicate that it may increase the risk of stillbirth and neonatal asphyxia. Antenatal use of uterotonics, even without the required fetal monitoring and prompt access to cesarean section, is widespread, yet no study has adequately estimated the risk of intrapartum stillbirth and early neonatal deaths ascribed to such use. We conducted a case-control study to estimate this risk.

Liquid mycobacterial culture outcomes after different sputum collection techniques before and during treatment.

Setting: Mycobacterial sputum culture is a key diagnostic and research tool.

Objective: To compare mycobacterial culture outcomes of three sputum collection methods.

Design: We compared culture results within sets of three sputum samples collected from 18 HIV-infected adult tuberculosis patients at regular intervals up to 84 days after treatment initiation.

Quantification of viable bacterial load in artificial sputum spiked with Mycobacterium tuberculosis.

Objective: Artificial sputum spiked with Mycobacterium tuberculosis could serve for validation of procedures that determine viable mycobacterial load.

Design: Artificial sputum specimens prepared in-house were spiked with low, medium or high concentrations of Mycobacterium tuberculosis H37Rv stock solution. In a first series, a single technologist processed two batches of specimens daily with high load that were stored refrigerated or at room temperature for up to 8 days.

Growth Inhibition Assay of Human Alveolar Macrophages as a Correlate of Immune Protection Following Mycobacterium bovis Bacille Calmette-Guérin Vaccination.

Background: In order to eliminate tuberculosis (TB), an effective vaccine is urgently needed to prevent infection with . A key obstacle for the development of novel TB vaccines is the lack of surrogate markers for immune protection against .

Methods: We investigated growth rates of in the mycobacterial growth inhibition assay (MGIA) as a marker for mycobacterial growth control of human bronchoalveolar lavage (BALC) and peripheral blood mononuclear cells (PBMC) before and after vaccination with Bacille Calmette-Guérin (BCG) of healthy adult volunteers.

Modification of the association between antipsychotic treatment response and childhood adversity by MMP9 gene variants in a first-episode schizophrenia cohort.

Antipsychotics remain the most effective, and wide used option for ameliorating the symptoms of schizophrenia. However, inter-individual differences in treatment outcome are vast and suggest a role for genetic and environmental factors in affording favourable outcomes. A notable epigenetic relationship which has gained considerable traction in recent literature is the way in which the severity of childhood trauma can modify associations seen between genetic variation and antipsychotic treatment response.

Association between pro-inflammatory alleles and allergic phenotypes in Xhosa adolescents.

Background: Significant differences exist in the prevalence, spectrum, and severity of allergic diseases between developing and developed countries and between subpopulations within single countries. These discrepancies likely result from a complex interaction between genetic and environmental factors. However, the precise nature of the contribution of ethnicity to genetic differences in the predisposition to allergic disease is not yet fully understood.

Pulmonary immune responses to Mycobacterium tuberculosis in exposed individuals.

Background: Blood based Interferon-(IFN)-γ release assays (IGRAs) have a poor predictive value for the development of tuberculosis. This study aimed to investigate the correlation between IGRAs and pulmonary immune responses in tuberculosis contacts in Germany.

Methods: IGRAs were performed on bronchoalveolar lavage (BAL) cells and peripheral blood from close healthy contacts of patients with culturally confirmed tuberculosis.

Hypothalamic-pituitary-adrenal axis variants and childhood trauma influence anxiety sensitivity in South African adolescents.

Anxiety sensitivity (AS) is characterised by the fear of anxiety-related symptoms and is a risk factor for the development of anxiety-related disorders. We examined whether genetic variation in three stress response genes, CRHR1, NR3C1, and FKBP5, interact with childhood trauma (CT) to predict AS in South African adolescents. Xhosa (n = 634) and Coloured (n = 317) students completed self-report measures of AS and CT, and a total of eighteen polymorphisms within CRHR1, NR3C1, and FKBP5 were genotyped.

Clinical Overestimation of HER2 Positivity in Early Estrogen and Progesterone Receptor-Positive Breast Cancer and the Value of Molecular Subtyping Using BluePrint.

Purpose: Human epidermal growth factor receptor 2 (HER2) positivity is an important prognostic and predictive indicator in breast cancer. HER2 status is determined by immunohistochemistry and fluorescent in situ hybridization (FISH), which are potentially inaccurate techniques as a result of several technical factors, polysomy of chromosome 17, and amplification or overexpression of CEP17 (centromeric probe for chromosome 17) and/or HER2. In South Africa, HER2-positive tumors are excluded from a MammaPrint (MP; Agendia BV, Amsterdam, Netherlands) pretest algorithm.

Acquisition of Rifampin Resistance in Pulmonary Tuberculosis.

strains with spontaneous mutations conferring resistance to rifampin (RIF) are exceedingly rare, and fixed drug combinations typically prevent augmentation of resistance to single drugs. Fourteen newly diagnosed tuberculosis patients were treated with RIF alone for 14 days, and bacterial loads, including mutation frequencies, were determined. A statistical model estimated that 1% of the remaining viable mycobacteria could be RIF resistant after 30 days of monotherapy.

Time Trends in Sputum Mycobacterial Load and Two-Day Bactericidal Activity of Isoniazid-Containing Antituberculosis Therapies.

Recent early bactericidal activity (EBA) studies of isoniazid-based antituberculosis therapies have shown a lower EBA over the first two treatment days than in earlier years. To quantify this trend and evaluate factors contributing to it, we extracted individual data from 18 studies with a total of 182 participants using isoniazid-containing therapies between 1992 and 2015 at a single site and laboratory in Cape Town, South Africa. We recalculated EBA as the daily fall in CFU per milliliter sputum up to day 2 of therapy (EBA) for individual patients and treatment groups and used mixed-effects linear models to investigate the correlation between pretreatment CFU, EBA, and year of study.

Fine-mapping of antipsychotic response genome-wide association studies reveals novel regulatory mechanisms.

Aim: Noncoding variation has demonstrated regulatory effects on disease treatment outcomes. This study investigated the potential functionality of previously implicated noncoding variants on schizophrenia treatment response.

Materials & Methods: Predicted regulatory potential of variation identified from antipsychotic response genome-wide association studies was determined.

Propidium monoazide and Xpert MTB/RIF to quantify Mycobacterium tuberculosis cells.

Propidium monoazide (PMA) penetrates non-viable cells with compromised membranes. PMA has been proposed to improve the specificity of Xpert MTB/RIF (Xpert) for the detection of viable Mycobacterium tuberculosis. This study assessed the effect of PMA on Xpert cycle thresholds (C) of M.

Impact of MammaPrint on Clinical Decision-Making in South African Patients with Early-Stage Breast Cancer.

The aim of the study was to evaluate the impact of MammaPrint on treatment decision-making in patients with breast cancer. Clinicopathologic information of all breast cancer patients referred for MammaPrint testing in South Africa was collected from 2007 until 2014. A total of 107 patients (109 tumors) with estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor-2 negative tumors were selected with tumors ≥10 mm, or when 1-3 nodes were involved without extra-nodal extension.

Altered Mitochondrial Respiration and Other Features of Mitochondrial Function in Parkin-Mutant Fibroblasts from Parkinson's Disease Patients.

Mutations in the parkin gene are the most common cause of early-onset Parkinson's disease (PD). Parkin, an E3 ubiquitin ligase, is involved in respiratory chain function, mitophagy, and mitochondrial dynamics. Human cellular models with parkin null mutations are particularly valuable for investigating the mitochondrial functions of parkin.

The identification of novel genetic variants associated with antipsychotic treatment response outcomes in first-episode schizophrenia patients.

Background: Although antipsychotics are integral to the treatment of schizophrenia, drug efficacy varies between patients. Although it has been shown that antipsychotic treatment response outcomes are heritable, our understanding of the genetic factors that are involved remains incomplete. Therefore, this study aims to use an unbiased scan of the genome to identify the genetic variants contributing toward antipsychotic treatment response outcomes.

CYP2B6*6 and CYP2B6*18 Predict Long-Term Efavirenz Exposure Measured in Hair Samples in HIV-Positive South African Women.

Long-term exposure to efavirenz (EFV) measured in hair samples may predict response to antiretroviral treatment (ART). Polymorphisms in CYP2B6 are known to alter EFV levels. The aim of this study was to assess the relationship between CYP2B6 genotype, EFV levels measured in hair, and virological outcomes on ART in a real-world setting.

Serotonin transporter variants play a role in anxiety sensitivity in South African adolescents.

Objectives: Anxiety sensitivity (AS) has predictive potential for the development of anxiety disorders. We investigated the role that gene-environment (G × E) interactions, focussing on childhood trauma (CT) and selected SLC6A4 variants, play in modulating levels of AS in a South African adolescent population.

Methods: All adolescents (n = 951) completed measures for AS and CT.